Biomarkers of epithelial-mesenchymal transition in localized, surgically treated clear-cell renal cell carcinoma

Gasińska, Anna; Jaszczyński, Janusz; Adamczyk, Agnieszka; Janecka-Widła, Anna; Wilk, Wacław; Cichocka, Anna; Stelmach, Andrzej

doi:10.5603/fhc.a2018.0023

Cited by 16 publications

(15 citation statements)

References 53 publications

(119 reference statements)

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“…The PI3K/AKT/mTOR pathway is altered in approximately 20% cases, by mutations in PIK3CA gene [107]. Next generation sequencing revealed the presence of PIK3CA gene mutations in RCC [108] but not in the clear cell subtype (cc-RCC), which is the major and most deadly RCC [109]. However, in a study that focused on cc-RCC, 20 components of the PI3K/AKT/mTOR pathway were analyzed by sequencing.…”

Section: The Importance Of Pik3ca Gene Mutations In Pathogenesis Of Rmentioning

confidence: 99%

PIK3CA Gene Mutations in Solid Malignancies: Association with Clinicopathological Parameters and Prognosis

Alqahtani

Ayesh

Halawani

2019

Cancers

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Phosphoinositide kinases (PIKs) are a group of lipid kinases that are important upstream activators of various significant signaling pathways. Hyperactivation of the PI3K/AKT/mTOR pathways—either via mutations or genomic amplification—confers key oncogenic activity, essential for the development and progression of several solid tumors. Alterations in the PIK3CA gene are associated with poor prognosis of solid malignancies. Although the literature reports contradictory prognostic values of PIK3CA in aggressive cancers, most of the available data highlight the important role of PIK3CA mutation in mediating tumorigenesis via increased signaling of the PI3K/AKT/mTOR survival pathway. Several inhibitors of PI3K/AKT/mTOR pathways are investigated as potential therapeutic options in solid malignancies. This article reviews the role of PIK3CA mutations and inhibitors of PI3K/AKT/mTOR pathways in major cancer types and examines its association with clinicopathological parameters and prognosis.

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Section: The Importance Of Pik3ca Gene Mutations In Pathogenesis Of Rmentioning

confidence: 99%

PIK3CA Gene Mutations in Solid Malignancies: Association with Clinicopathological Parameters and Prognosis

Alqahtani

Ayesh

Halawani

2019

Cancers

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“…PTEN [15], CR1 (complement C3b/C4b receptor 1, [16]), MERTK (MER proto-oncogene tyrosine kinase [17]), PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [18]) and AKT1 (AKT serine/threonine kinase 1 [19]) are among the most popular KC biomarkers. The PI3K/Akt pathway, one that is altered in several cancers, has been evaluated as a potential target for therapies [20].…”

Section: Introductionmentioning

confidence: 99%

Genomic Fabric Remodeling in Metastatic Clear Cell Renal Cell Carcinoma (ccRCC): A New Paradigm and Proposal for a Personalized Gene Therapy Approach

Iacobaş

Mgbemena

Iacobaş

et al. 2020

Preprint

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Published transcriptomic data from surgically removed metastatic clear cell renal cell carcinoma (ccRCC) samples were re-analyzed from the Genomic Fabric Perspective that considers the transcriptome a multi-dimensional mathematical object, constrained by a dynamic set of expression correlations among genes. Every gene in the chest wall metastasis (MET), two primary tumors (PTA, PTB) and the surrounding normal tissue (NOR) of the right kidney was characterized by three independent measures: average expression level (AVE), relative expression variation (REV) and expression correlation (COR) with each other gene. AVE was used to determine the regulation of the genomic fabrics of ccRCC, apoptosis, chemokine and VEGF signaling pathways. REV quantified the alteration of the transcripts’ abundances control, while COR determined the remodeling of the transcriptomic networks of chemokine signaling and oxidative phosphorylation genes. The gene hierarchy was established in based on Gene Commanding Height and the Gene Master Regulators (GMR) TASOR (PTA), FAM27C (PTB) and ALG13 (MET) and DAPK3 (NOR) were identified in each profiled region. We predict that TASOR overexpression would block transcription in PTA but not in PTB, while slightly stimulating it in NOR. Silencing of ALG3 would slow-down the cell-cycle in all three cancer regions with practically no effect in NOR.

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“…JPH203 inhibits the function of the LAT1 in many types of cancer cells, which functions through the mTOR signaling pathway to block their migration/invasion activities and induce apoptosis 13,21 . Additionally, JPH203 shows significant growth inhibition effects against xenografted human colon or biliary tract cancer cells 22,23 , and its efficacy has been reported in a clinical trial of several cancers 24,25 .…”

mentioning

confidence: 99%

Expression of L-type amino acid transporter 1 as a molecular target for prognostic and therapeutic indicators in bladder carcinoma

Maimaiti

Sakamoto

Yamada

et al. 2020

Sci Rep

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L-type amino acid transporter 1 (LAT1) plays a role in transporting essential amino acids including leucine, which regulates the mTOR signaling pathway. Here, we studied the expression profile and functional role of LAT1 in bladder cancer. Furthermore, the pharmacological activity of JPH203, a specific inhibitor of LAT1, was studied in bladder cancer. LAT1 expression in bladder cancer cells was higher than that in normal cells. SiLAT1 and JPH203 suppressed cell proliferative and migratory and invasive abilities in bladder cancer cells. JPH203 inhibited leucine uptake by > 90%. RNA-seq analysis identified insulin-like growth factor-binding protein-5 (IGFBP-5) as a downstream target of JPH203. JPH203 inhibited phosphorylation of MAPK / Erk, AKT, p70S6K and 4EBP-1. Multivariate analysis revealed that high LAT1 expression was found as an independent prognostic factor for overall survival (HR3.46 P = 0.0204). Patients with high LAT1 and IGFBP-5 expression had significantly shorter overall survival periods than those with low expression (P = 0.0005). High LAT1 was related to the high Grade, pathological T stage, LDH, and NLR. Collectively, LAT1 significantly contributed to bladder cancer progression. Targeting LAT1 by JPH203 may represent a novel therapeutic option in bladder cancer treatment.Bladder cancer (BC) is the ninth most common malignant tumour worldwide, with 430 000 patients newly diagnosed and 165 000 deaths annually 1 . The pathological type of BC is mainly urothelial cancer ( > 90%) and approximately 70% of patients had non-muscle-invasive BC at diagnosis 2 . These patients have a favorable prognosis with transurethral resection and subsequent intravesical injection therapy, whereas the survival rate of patients with locally advanced and metastatic BC is poor 3 . For metastatic BC patients, platinum-based systematic chemotherapy is the classical treatment, while immunotherapy targeting programmed cell death ligand 1 (PD-L1) blocking antibody was recently approved in Japan 4 . However, drug resistance will occur, and the survival benefit of these agents is not adequate. Their limited efficacy is due to side effects and challenges of drug resistance, leading to treatment failure and require additional treatment options 5 . Therefore, more effective and less toxic therapeutic strategies are needed for the treatment of metastatic BC. Additionally, there are presently no useful diagnostic markers for BC. The urine cytology test is a non-invasive examination, but its sensitivity remains low. Cystoscopy is an essential diagnostic tool but is invasive for patients 5 . Thus, a novel therapeutic approach and biomarker candidates for BC remain a major issue.

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Biomarkers of epithelial-mesenchymal transition in localized, surgically treated clear-cell renal cell carcinoma

Cited by 16 publications

References 53 publications

PIK3CA Gene Mutations in Solid Malignancies: Association with Clinicopathological Parameters and Prognosis

PIK3CA Gene Mutations in Solid Malignancies: Association with Clinicopathological Parameters and Prognosis

Genomic Fabric Remodeling in Metastatic Clear Cell Renal Cell Carcinoma (ccRCC): A New Paradigm and Proposal for a Personalized Gene Therapy Approach

Expression of L-type amino acid transporter 1 as a molecular target for prognostic and therapeutic indicators in bladder carcinoma

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